title: Association between mRNA levels of DNMT1, DNMT3A, DNMT3B, MBD2 and LINE-1 methylation status in infants with tetralogy of Fallot.
abstract: DNA methylation is catalyzed and maintained by DNA methyltransferases (DNMTs: DNMT1, DNMT3A and DNMT3B) and methyl-CpG-binding domain protein 2 (MBD2). However, little is known about the biological and clinical significance of the expression changes of DNMTs and MBD2 and their association with the methylation levels of long interspersed nuclear element-1 (LINE-1) in patients with tetralogy of Fallot (TOF). In this study, quantitative RT-PCR (qRT-PCR) was applied to analyze the mRNA levels of DNMTs and MBD2. The methylation status of LINE-1 was measured using the sequenom MassARRAY platform. The mRNA levels of the DNMTs and MBD2 showed a statistically significant decrease in the patients with TOF (P<0.001). The results also showed that patients with TOF had significantly lower global DNA methylation levels with a median of 61.50% [interquartile range (IQR), 59.78-63.77] compared with 63.54% (IQR, 62.49‑64.88) among the controls (P=0.0099). In the controls, only DNMT1 showed a significant positive correlation with the DNMT3A mRNA levels (r=0.718, P=0.002). Of note, the DNMT1, DNMT3A, DNMT3B and MBD2 mRNA levels positively correlated with each other; this was statistically significant (P<0.05). A significant positive correlation with the global DNA methylation status was observed only for MBD2 (r=-0.579, P=0.005) in patients with TOF. In conclusion, lower LINE-1 methylation levels significantly correlate with aberrant MBD2 mRNA levels. The lower expression of DNMT1 and DNMT3B may play an important role in the pathogenesis of TOF.
authors.affiliation: Children's Hospital, Fudan University, Shanghai 201102, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sheng
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Qian
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.forename: Guoying
authors.initials: G
authors.lastname: Huang
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013771:Tetralogy of Fallot / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C115368:MBD2 protein; C000619380:DNMT1 protein, human